Tuesday, January 13, 2009

Pagoclone trial start in March

I just heard that the Pagoclone study will start in March at several center across the US. This info fits the press release from last year: The placebo-controlled study will involve approximately 300 patients with stuttering in the U.S. treated for a period of six months and is expected to commence enrollment by Q1 2009.

So we should not expect any results until March next year earliest. Six months treatment period plus at least 3 months logistics (i.e. not everyone will be enrolled on same day) plus 3 months analysis time, and maybe a few months of observation time.

Here is my prediction: If they are good scientists, they will get a null or minor impact result above placebo and repeated measurement effect. If they are bad scientists, they will get a moderate result good enough to market the compound for stuttering. However, they might be able to show that it has a good impact in some people, but they then must convince me that this is not a random effect.

20 comments:

Tom - You wrote: "Here is my prediction: If they are good scientists, they will get a null or minor impact result above placebo and repeated measurement effect"?

Can you explain why you say that, in light of the statistically significant results in the original Level 2 trials and the open-label extension?

Maybe you're saying that the effect size was small or unspecified? (I think the results were most recently presented at the Oxford Dysfluency Conference in July 2008, but I don't recall exactly what that report said about effect size.)

It's worth recognizing that all the participants in the Phase 2 trials had the same standard dosage level, while the Phase 3 trials are an opportunity to try multiple doses and determine whether other dosage levels are more effective than the standard Phase 2 dose. It's quite plausible that optimizing the dosage will allow some increase in benefit.

Even though these trials are double-blind, I don't think it's possible to determine the real effect of the placebo. Here's what I mean: group 1 is given pagoclone and group 2 is given sugar tablets. The people in group 1 feel somewhat different after taking the medication, so some of them might be convinced that they have the pagoclone. This means that they might subconsciously convince themselves that they are taking an effective drug, and their fluency will improve accordingly. The people in group 2 may not feel any effect of any medication (although they may imagine it), but some of them might nevertheless *believe* that they are taking pagoclone, and their fluency might improve as a consequence. The placebo effect is very powerful.How to sort placebo effect from drug effect is a big problem, and I don't believe it can be resolved - no matter how professional the researchers are. For all we know, the placebo effect alone is the only factor that contributes to the improvement in fluency.

in stuttering there shouldn't be placebo, because the problem is psychological.. and the placebo may be (and is) treated like psychological medication. It means that this placebo, really helps like real pill! Thus, we have 2 groups... one that took pagoclone, and other that took sort of artificial self confidence (which may have effect equal like the pagoclone).

So, the real test would be to give to some group pagoclone (not placebo), and after that to be told that group that they took placebo, so the exaltation effect pass by, and the real pagoclone benefits come on surface

>> Even though these trials are double-blind, I don't think it's possible to determine the real effect of the placebo. Here's what I mean: group 1 is given pagoclone and group 2 is given sugar tablets. The people in group 1 feel somewhat different after taking the medication, so some of them might be convinced that they have the pagoclone. This means that they might subconsciously convince themselves that they are taking an effective drug, and their fluency will improve accordingly. The people in group 2 may not feel any effect of any medication (although they may imagine it), but some of them might nevertheless *believe* that they are taking pagoclone, and their fluency might improve as a consequence. The placebo effect is very powerful.

I specifically asked Jerry about this, and he said that they did tests and that the subjects were not very good at predicting whether they were on the compound or not.

This seems reasonable to me because the side effects of Pagoclone are small.

Weidig's "prediction" re outcomes of the pagaclone trials might be based on his apparent bias against drug therapies (wishful thinking for drug test failure). Apparently, he's spent too much time in traditional speech therapies and has come to accept his affliction as "normal"

>> Weidig's "prediction" re outcomes of the pagaclone trials might be based on his apparent bias against drug therapies (wishful thinking for drug test failure). Apparently, he's spent too much time in traditional speech therapies and has come to accept his affliction as "normal"

You make a statement about my attitude even though you don't know me. Of course, I would be happy to take a medication that decreases noticeably my stuttering assuming I have no unacceptable costs like side effects and long-term (mental) health issues.

My affliction is of course not normal, but I do accept that my brain will ALWAYS have more trouble speaking fluently. And I need to do something to compensate either behavioural therapy or medication or something else.

My prediction is based on my experience as a professional scientists and interaction with other scientists at leading university.

Moreover, it is a healthy attitude to prepare for the worse rather than go into a trial trying to prove something.

Tom - you wrote "Of course, I would be happy to take a medication that decreases noticeably my stuttering assuming I have no unacceptable costs like side effects and long-term (mental) health issues."

You know that there are such medications out there. Jerry Maguire has done research on Zyprexa (olanzapine), and has a published case report on Abilify (aripiprazole). He's sufficiently comfortable with olanzapine and Geodon (ziprasidone) that he's taken them himself for years. (Olanzapine for 10 years, Geodon for the past 2.) In addition, he's prescribing them to patients.

Have you considered trying them for yourself and see your reaction? What's your objection to trying them?

I don't mean to be challenging to you or to ask an overly personal question - this is a very personal issue, of course. But I'd be interested in your thoughts on this issue.

So, the real test would be to give to some group pagoclone (not placebo), and after that to be told that group that they took placebo, so the exaltation effect pass by, and the real pagoclone benefits come on surfaceNo. You'd need to give Pagoclone to a group of stammerers without telling them about it. You could do this by, for example, identifying stammerers who had an unrelated condition (eg. a skin condition) and get them to sign the Pagoclone disclaimer on that basis.

This is going to be tricky, especially since they need to be undergoing stammering treatment at the same time (so you can monitor fluency). But you may find a sufficiently large population in some metropolitan areas.

Hi, I just quit Pagaclone trial after two failed attempts to persevere. From my experience with the drug it felt that Pagaclone is a generalized CNS depressant that affects many brain functions besides speech production and anxiety. I felt difficulty concentrating on the tasks at hand and could not plan and execute many ADLs as usual. I required at least an extra hour of sleep a day (that was actually good). As for the speech itself, I think I stuttered in a more pronounced way but could not care less about it (actually did not care about anything much). For me, intellectual, spiritual and emotional castration did not feel like a fair trade off for not feeling the pain of stuttering.

Actually, that depressing the CNS sounds good to me. I am looking at Pagaclone as a possible anti-anxiety agent that would help desensitize me, and others with panic disorder, OCD, and other anxiety disorders. Let me tell you, after being oversensitized, freaking out at sounds, visuals, etc., emotional dulling sounds like a slice of heaven for awhile.

Right now I am taking Xanax and adding Benedryl to it for relief, but the Dr. is pushing for another SSRI. I just don't want all that comes with that again. It's hell.

Chronic Xanax use tends to sensitize one to anxiety. This is noticed when one misses a dose. It is due to tolerance effects.

It does help to learn meditation when medicated, mainly to learn techniques to deal with stress due to detoxifying from meds, especially when switching to a new medication.

Don't ever believe your doctor when he claims your symptoms are due to the illness rather than the meds.

Xanax is addictive, as is Benadryl and most SSRIs (except they use a synonym for 'addiction').

We know methamphetamines are addictive, yet we prescribe them to children for ADD, mainly to prevent future drug abuse than anything else.

Since our society desires focused children who excess academically rather than sociable and emotionally intelligent children, stimulants will always be in demand both by the workplace (coffee) and recreationally.

Meanwhile, marijuana is demonized, mainly because THC intoxication is associated with sociability.

But if I had a choice between a tweaker and a pothead, I'd choose the pothead.